HBV RNA Profiles in Patients With Chronic Hepatitis B Under Different Disease Phases and Antiviral Therapy

Hepatology. 2021 Jun;73(6):2167-2179. doi: 10.1002/hep.31616.


Background and aims: Large-scale comprehensive studies on HBV RNA in chronic hepatitis B are lacking. We aimed to study the HBV RNA profile and its correlation with other viral markers in patients with chronic hepatitis B who are treatment-naïve and patients receiving nucleos(t)ide analogues (NA).

Approach and results: Biomarkers, including HBV RNA and hepatitis B core-related antigen (HBcrAg), were measured in 388 patients. Of these, 246 were treatment-naïve and were categorized into HBeAg-positive chronic infection (n = 41), HBeAg-positive chronic hepatitis (n = 81), HBeAg-negative chronic infection (n = 39), HBeAg-negative chronic hepatitis (n = 66), and HBsAg seroclearance (n = 19). These biomarkers were also measured in 142 patients who were NA-treated receiving tenofovir or entecavir at baseline, week 48, and week 96. The pattern of serum HBV RNA levels mirrored HBV DNA (1-2 logs higher than HBV RNA) and HBcrAg in patients who were treatment-naïve. HBV RNA correlated best with HBcrAg (r = 0.84) and to a lesser extent with HBV DNA (r = 0.737) (both P < 0.001). In patients with HBsAg seroclearance, 15.8% and 15.8% had detectable serum HBV RNA and HBcrAg, respectively. NA treatment reduced serum HBV RNA by 1.46 logs and 1.77 logs at weeks 48 and 96, respectively. At week 96 of NA therapy, only 19.1% patients who were tenofovir-treated and 25.7% patients who were entecavir-treated had unquantifiable HBV RNA (P > 0.05). In patients who were treated and had undetectable HBV DNA, 77.5% and 30% had quantifiable HBV RNA and HBcrAg, respectively.

Conclusions: HBV RNA showed distinct and corresponding profiles in patients with HBV in different disease phases. HBV RNA and HBcrAg could be used to monitor residual transcriptional activities in patients with HBsAg seroclearance. NA led to reduction of serum HBV RNA. Monitoring of viral activities can still be achieved in patients with undetectable HBV DNA by serum HBV RNA.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Female
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B Core Antigens / blood*
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Hong Kong
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood*
  • Tenofovir / therapeutic use
  • Treatment Outcome


  • Antiviral Agents
  • Biomarkers
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • RNA, Viral
  • entecavir
  • Guanine
  • Tenofovir